Curcumin is known to interrupt pro-inflammatory signalling and increases anti-oxidant protection, thus inhibiting the expression of inflammatory cytokines and the expression and function of inducible inflammatory enzymes. Together, these effects contribute to limit the onset and the progression of sarcopenia, due to the major role played by inflammation in the pathophysiology of this disease. This registry study evaluates the effects of Meriva\uae supplementation in otherwise healthy elderly subjects

Belcaro, G.

Cornelli, U

Eggenhoffner, R

Feregalli, B

Franceschi, F

Giacomelli, L

Togni, S

English

Curcumin is known to interrupt pro-inflammatory signalling and increases anti-oxidant protection, thus inhibiting the expression of inflammatory cytokines and the expression and function of inducible inflammatory enzymes. Together, these effects contribute to limit the onset and the progression of sarcopenia, due to the major role played by inflammation in the pathophysiology of this disease. This registry study evaluates the effects of Meriva® supplementation in otherwise healthy elderly subjects

Archivio istituzionale della ricerca - Università di Genova

European Review for Medical and Pharmacological Sciences762Abstract. – OBJECTIVE: Curcumin is knownto interrupt pro-inflammatory signalling and in-creases anti-oxidant protection, thus inhibitingthe expression of inflammatory cytokines andthe expression and function of inducible inflam-matory enzymes. Together, these effects con-tribute to limit the onset and the progression ofsarcopenia, due to the major role played by in-flammation in the pathophysiology of this dis-ease. This registry study evaluates the effects ofMeriva® supplementation in otherwise healthyelderly subjects.PATIENTS AND METHODS: This was a reg-istry, supplement study, conducted in healthysubjects > 65 years with apparent loss ofstrength and tiredness who freely decided tostart one of the following interventions: (1) stan-dard management (exercise, balanced diet in-cluding proteins) (n = 33); (2) standard manage-ment + Meriva® one tablet/day (n = 31); (3) stan-dard management + Meriva® one tablet/day +other supplementation (n = 22). A number offunctional and biochemical parameters wereevaluated at baseline and after three months(hand grip, weight lifting, time/distance beforefeeling tired after cycling, walking and climbingstairs; general fitness, proteinuria, oxidativestress, Karnofsky scale; left ventricular ejectionfraction).RESULTS: Significant improvements in all pa-rameters, with respect to baseline values, wereobserved in the two supplementation groups (p< 0.05 for all comparisons). On the other hand,no improvement was observed in the standardmanagement-only group. At three months, inter-group comparison revealed a statistical advan-tage in all parameters for both supplementationgroups compared with the standard manage-ment-only group (p < 0.05 for all comparisons).CONCLUSIONS: Our registry study showsthat the addition of Meriva® – either or not com-bined with other nutritional supplements – tostandardized diet and exercise plan contributesA novel phospholipid delivery system ofcurcumin (Meriva®) preserves muscularmass in healthy aging subjectsF. FRANCESCHI1, B. FEREGALLI2, S. TOGNI1, U. CORNELLI2,L. GIACOMELLI3, R. EGGENHOFFNER3, G. BELCARO21Indena S.p.A, Milan, Italy2Irvine 3 Labs, Pescara, Italy3Department of Surgical Sciences and Integrated Diagnostics, School of Medicine, Genova University,Genoa, ItalyCorresponding Author: Federico Franceschi, Ph.D; e-mail: Federico.franceschi@indena.comto improve strenght and physical performancein elderly subjects, potentially preventing theonset of sarcopenia.Key Words:Curcumin, Meriva®, Nutritional supplementation,Registry, Sarcopenia.IntroductionSarcopenia is a decrease in muscle mass oftenrelated with age or pathological conditions1,2.Due to increasing age of population, the preva-lence of sarcopenia is increasing in Westerncountries. Moreover, sarcopenia can progress inits severity and impair the ability to performdaily acrivities, with a marked impact on quali-ty of life1,2. Eventually, sarcopenia may lead toan increased risk of disability, falls and hospital-ization3.Besides life style-related factors, as diet andphysical activity, other mechanisms underlyingthe development of sarcopenia are not complete-ly understood. However, they are thought to bemulti-factorial, with chronic inflammation statusplaying a crucial role4. Nutritional interventions may provide an im-portant contribution to prevent the developmentof sarcopenia1. Among different nutritional inter-ventions, curcumin is known to exert a pleiotrop-ic effect. Curcumin interrupts pro-inflammatorysignalling and increases anti-oxidant protectionby acting at distinct time-domain targets: (1)short time-domain targets such as pro-inflamma-tory enzymes (mPGES-1, 5-LO), and ion chan-nels (TRPV1, TRPA1), and (2) long time-do-main targets such as pro-inflammatory transcrip-2016; 20: 762-766763Meriva in healthy elderly subjectsEndurance Cycling/Walinkg/Climbing stairs until exaustion DailyStrenght Lifting low weights 20 × arm, 20 × leg, three times dailyBalance Walk along a 5-meter line DailyFlexibility All main joints 20 second×joint, twice dailyTable I. Exercise program, performed every day.decided, after consultation at our Center for ap-parent loss of strength and tiredness, to start oneof the following interventions: (1) standard man-agement: exercise (Table I), balanced diet in-cluding proteins (both according to the instruc-tions of trained specialists); (2) Group B: stan-dard management + Meriva® one tablet/day(each tablet containing 1 g Meriva®); (3) stan-dard management + Meriva® one tablet/day +other supplementation (Vitamin D 800 IU/day;Vitamin C 500 mg/day; Isoleucin 3 g/day;Carinitine 1 g/day). The participants were visitedat baseline and after three months. No othertreatments were needed or used during the obser-vation period. All patients had a completely no-mal cardiovascular system (as shown by ultra-sound evaluation before inclusion).The following evaluations were performed atbaseline and at the end of the observation period:(1) hand grip, using standard digital Jamar dy-namometers (Patterson Medical, Warrenvile, IL,USA) and assessed as the sum of three consecu-tive measurements in 1 minute; (2) weight lift-ing, assessed as the number of times the subjectcan lift a 2 kg manuber; (3) time/distance beforefeeling tired after cycling, walking and climbingstairs; (4) general fitness, by a numerical scale (0= unable to move; 3 = normal); (5) proteinuria;(6) oxidative stress measurements, accordingto24,25; (7) Karnofsky scale; (8) measurement ofleft ventricular ejection fraction by ultrasounds.Basic blood tests and the physiological para-meters were also evaluated at inclusion and at theend of the observational period.Statistical AnalysisData were analyzed by descriptive statistics.Intra- and inter-group comparisons were per-formed by the Mann-Witney test. A p value <0.05 was considered statistically significant.ResultsIn total, 86 registry subjects were followed up.Of these, 33 decided to follow standard manage-tion factors (NF-kB, AP1, STAT, PPAR-g). As anet result, curcumin inhibits the expression of in-flammatory cytokines (TNF-a, IL-1b, IL-6) andof the expression and function of inducible in-flammatory enzymes (COX2 and mPG2S)5-7. Inparticular, NF-kB is involved in the developmentof muscle wasting during catabolic conditionssuch as sarcopenia; animal studies have shownthat inhibition of NF-kB activity in skeletal mus-cle allows reducing protein degradation8. A simi-lar effect is associated with the inhibition of oth-er pro-inflammatory enzymes exerted by cur-cumin8. Moreover, curcumin contributes to re-duce the inflammatory burden leading to muscleloss in sarcopenia patients by inducing an inhibi-tion of p38 kinase activity, oxygen radical scav-enging, and induction of the heat-shock re-sponse8. Together, these effects, and in particularthe inhibition of NF-kB, do contribute to limitthe onset and the progression of sarcopenia8.However, curcumin has a poor systemicbioavailability9. Several attempts have beenmade to overcome this limitation: in particular,dispersion of active molecules (typically belong-ing to the chemical class of polyphenols andtriterpenes) with phospholipids under appropriateconditions leads to the formation of a deliveryform named Phytosome®10. Among these com-plexes, the commercially available Phytosome®of curcumin, named Meriva®, has been studiedfor the treatment of a wide range of conditionscompared versus non-formulated Curcumin11-22.On these bases, curcumin may represent a po-tential nutritional intervention to control sarcope-nia in affected subjects, in particular for elderly.This registry study evaluates the effects of Meri-va® supplementation in otherwise healthy elderlysubjects, in order to preliminarily evaluate its ef-ficacy in the management of sarcopenia.Patients and MethodsThis was a registry, supplement study (see23for a complete description of such studies), con-ducted in healty subjects > 65 years who freely764F. Franceschi, B. Feregalli, S. Togni, U. Cornelli, L. Giacomelli, R. Eggenhoffner, G. Belcaroment only, 31 standard management+Meriva®and 22 took also the additional supplementation.No significant differences among groups werereported (Table II). No safety concerns or clini-cally relevant variations of laboratory parametersand vital signs were reported.Table III summarizes the efficacy evaluations.Overall, significant improvements in all parame-ters, with respect to baseline values, were ob-served in the two supplementation groups; on theother hand, no improvement was observed in thestandard management only group. At threemonths, inter-group comparison revealed a statis-tical advantage in all parameters for both supple-mentation groups compared with the standardmanagement only group.Compliance to supplementation was good withmore than 95% of the supplements correctly used.DiscussionSarcopenia represents a major clinical issue,given also the increasing prevalence of elderlypeople in the general population. This clinicalcondition can lead to a number of health prob-lems, with a significant burden to the healthcaresystem. It has been proposed that nutritional supple-mentation can have a role in the prevention andmanagement of sarcopenia1. Our registry study,conducted in healty elderly subjects complainingfor strength loss and physical tiredness, lendsfurther support to this assumption. In fact, the addition, to standardized diet andexercise, of nutritional supplementation withMeriva®, either or not combined with other sup-plements, resulted in statistically significant andStandardStandard Standard management + Meriva® +management only management + Meriva® additional supplementationSubjects 33 31 22Females 16 14 12Age, years (mean ± SD) 72 (2) 74 (1) 73 (1)BMI, kg/m2 24.7 (1.0) 24.3 (1.5) 24.3 (1.2)Table II. Basline characteristics.SD: standard deviation.StandardStandard Standard management + Meriva® +management only management + Meriva® additional supplementation(n = 33) (n = 31) (n = 22)Baseline 3 months Baseline 3 months Baseline 3 monthsHand grip, kg 32.2 (2.1) 31.8 (2.0) 31.2 (1.5) 33.9 (1.8)* 32.8 (1.7) 35.4 (1.1)*Weight lifting 12 (2) 11 (1) 13 (1) 16 (2)* 11 (1) 16 (2)*Time/distance beforeeeling tired, minutes(meters for the walkingtest)Cycling 2’ 20” (18”) 2’ 16” (12”) 2’ 29” (18”) 3’ 11” (11”)* 2’ 14” (13”) 3’ 44” (21”)*Walking 234 (21) 239 (12) 251 (11) 311 (14)* 244 (18) 319 (24)*Climbing stairs 58” (6”) 69” (5”) 54” (6”) 75” (3”)* 51” (5”) 69” (2”)*General fitness, score 1.1 1.1 1.2 2.2* 1.1 2.5*Proteinuria, mg/die 244 (37) 239 (46) 239 (28) 154 (39)* 233 (34) 158 (39)*Oxidative stress, carr units 368 (24) 359 (26) 379 (31) 334 (26)* 377 (28)* 336 (23)*Karnofsky scale, units 75.4 (3.2) 72.2 (1.3) 76.2 (3.4) 81.1 (2.0)* 75.3 (1.8) 83.4 (2.2)*Left ventricular 54.8 (0.2) 55 (0.4) 56.2 (0.5) 59.8 (0.3)* 57.1 (0.6) 62.4 (1.0)*ejection fraction, %Table III. Efficacy evaluations. All data are expressed as mean (SD).*p < 0.05 vs. baseline and vs. standard management-only.clinically relevant improvements in a number offunctional and physiological parameters withoutany safety concern. On the other hand, stardardmanagement only was not associated with any sig-nificant improvement over a 3 months’ period. Our findings can be due, at least in part, to therecognized anti-inflammatory effects of Meri-va®5,6,8, which target systemic inflammation, oneof the main contributors to the onset of sarcope-nia4. Moreover, in animal models curcumin wasshown to promote protein regeneration and re-duce muscle loss26.Remarkably, subjects who decided to takesupplementation reported a reduction of oxida-tive stress, which remains a major determinant ofsarcopenia development. This kind of cellulardamage has a role in enhancing tiredness andweakness, also in healty subjects27,28, overall po-tentially contributing to the onset of sarcopenia.Further studies on the effect of oxidative stressand anti-oxidant compounds in sarcopenia pa-tients can be of the highest interest. Moreover,the effects of nutritional supplementation werealso evident in improving left ventricular ejectionfraction: while all subjects had normal values ofthis parameter at baseline, this finding may sug-gest more specific studies in patients with im-paired left ventricular function.ConclusionsOur registry study shows that the addition ofMeriva® – either or not combined with other nu-tritional supplements – to standardized diet andexercise plan contributes to improve strenght andphysical performance in elderly subjects, poten-tially preventing the onset of sarcopenia. We be-lieve that Meriva®, in the context of an integratedapproach29-33, holds the potential to have a role inthe management of this condition.–––––––––––––––––-–––Conflict of InterestFF and ST are employees of Indena S.p.A. LG is a consul-tant of Indena S.p.A.References1) YANAI H. Nutrition for sarcopenia. J Clin Med Res2015; 7: 926-931.2) YU S, UMAPATHYSIVAM K, VISVANATHAN R. Sarcopeniain older people. Int J Evid Based Health 2014; 12:227-243.765Meriva in healthy elderly subjects3) ROLLAND Y, DUPUY C, ABELLAN VAN KAN G, GILLETTE S,VELLAS B. Treatment strategies for sarcopenia andfrailty. Med Clin North Am 2011; 95: 427-438, ix.4) BUDUI SL, ROSSI AP, ZAMBONI M. The pathogeneticbases of sarcopenia. Clin Cases Miner BoneMetab 2015; 12: 22-26.5) GUPTA SC, PATCHVA S, AGGARWAL BB. Therapeuticroles of curcumin: lessons learned from clinicaltrials. AAPS J 2013; 15: 195-218.6) ZHOU H, BEEVERS CS, HUANG S. The targets of cur-cumin. 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A novel phospholipid delivery system of curcumin (Meriva®) preserves muscular mass in healthy aging subjects

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A novel phospholipid delivery system of curcumin (Meriva\uae) preserves muscular mass in healthy aging subjects

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Archivio istituzionale della ricerca - Università di Genova